Literature DB >> 27994757

Discovery of Pyrazolopyrimidine Derivatives as Novel Dual Inhibitors of BTK and PI3Kδ.

Brahmam Pujala1, Anil K Agarwal1, Sandip Middya2, Monali Banerjee2, Arjun Surya2, Anjan K Nayak1, Ashu Gupta1, Sweta Khare1, Rambabu Guguloth1, Nitin A Randive1, Bharat U Shinde1, Anamika Thakur1, Dhananjay I Patel1, Mohd Raja1, Michael J Green3, Jennifer Alfaro4, Patricio Avila4, Felipe Pérez de Arce5, Ramona G Almirez3, Stacy Kanno3, Sebastián Bernales3, David T Hung3, Sarvajit Chakravarty3, Emma McCullagh3, Kevin P Quinn3, Roopa Rai3, Son M Pham3.   

Abstract

The aberrant activation of B-cells has been implicated in several types of cancers and hematological disorders. BTK and PI3Kδ are kinases responsible for B-cell signal transduction, and inhibitors of these enzymes have demonstrated clinical benefit in certain types of lymphoma. Simultaneous inhibition of these pathways could result in more robust responses or overcome resistance as observed in single agent use. We report a series of novel compounds that have low nanomolar potency against both BTK and PI3Kδ as well as acceptable PK properties that could be useful in the development of treatments against B-cell related diseases.

Entities:  

Keywords:  B-cell; BCR; BTK; PI3K; inhibitor; p110δ; pyrazolopyrimidine

Year:  2016        PMID： 27994757      PMCID： PMC5150666          DOI： 10.1021/acsmedchemlett.6b00356

Source DB:  PubMed          Journal:  ACS Med Chem Lett        ISSN： 1948-5875            Impact factor:   4.345


  17 in total

1.  Discovery of selective irreversible inhibitors for Bruton's tyrosine kinase.

Authors:  Zhengying Pan; Heleen Scheerens; Shyr-Jiann Li; Brian E Schultz; Paul A Sprengeler; L Chuck Burrill; Rohan V Mendonca; Michael D Sweeney; Keana C K Scott; Paul G Grothaus; Douglas A Jeffery; Jill M Spoerke; Lee A Honigberg; Peter R Young; Stacie A Dalrymple; James T Palmer
Journal:  ChemMedChem       Date:  2007-01       Impact factor: 3.466

2.  FDA approval: idelalisib monotherapy for the treatment of patients with follicular lymphoma and small lymphocytic lymphoma.

Authors:  Barry W Miller; Donna Przepiorka; R Angelo de Claro; Kyung Lee; Lei Nie; Natalie Simpson; Ramadevi Gudi; Haleh Saber; Stacy Shord; Julie Bullock; Dhananjay Marathe; Nitin Mehrotra; Li Shan Hsieh; Debasis Ghosh; Janice Brown; Robert C Kane; Robert Justice; Edvardas Kaminskas; Ann T Farrell; Richard Pazdur
Journal:  Clin Cancer Res       Date:  2015-02-02       Impact factor: 12.531

3.  Ibrutinib and idelalisib synergistically target BCR-controlled adhesion in MCL and CLL: a rationale for combination therapy.

Authors:  Martin F M de Rooij; Annemieke Kuil; Arnon P Kater; Marie José Kersten; Steven T Pals; Marcel Spaargaren
Journal:  Blood       Date:  2015-04-02       Impact factor: 22.113

Review 4.  New insights into pre-BCR and BCR signalling with relevance to B cell malignancies.

Authors:  Robert C Rickert
Journal:  Nat Rev Immunol       Date:  2013-08       Impact factor: 53.106

5.  PI3K and Btk differentially regulate B cell antigen receptor-mediated signal transduction.

Authors:  Harumi Suzuki; Satoshi Matsuda; Yasuo Terauchi; Mari Fujiwara; Toshiaki Ohteki; Tomoichiro Asano; Timothy W Behrens; Taku Kouro; Kiyoshi Takatsu; Takashi Kadowaki; Shigeo Koyasu
Journal:  Nat Immunol       Date:  2003-02-03       Impact factor: 25.606

6.  Evolution of ibrutinib resistance in chronic lymphocytic leukemia (CLL).

Authors:  Natalia L Komarova; Jan A Burger; Dominik Wodarz
Journal:  Proc Natl Acad Sci U S A       Date:  2014-09-08       Impact factor: 11.205

7.  Targeting BTK with ibrutinib in relapsed or refractory mantle-cell lymphoma.

Authors:  Michael L Wang; Simon Rule; Peter Martin; Andre Goy; Rebecca Auer; Brad S Kahl; Wojciech Jurczak; Ranjana H Advani; Jorge E Romaguera; Michael E Williams; Jacqueline C Barrientos; Ewa Chmielowska; John Radford; Stephan Stilgenbauer; Martin Dreyling; Wieslaw Wiktor Jedrzejczak; Peter Johnson; Stephen E Spurgeon; Lei Li; Liang Zhang; Kate Newberry; Zhishuo Ou; Nancy Cheng; Bingliang Fang; Jesse McGreivy; Fong Clow; Joseph J Buggy; Betty Y Chang; Darrin M Beaupre; Lori A Kunkel; Kristie A Blum
Journal:  N Engl J Med       Date:  2013-06-19       Impact factor: 91.245

8.  Targeting BTK with ibrutinib in relapsed chronic lymphocytic leukemia.

Authors:  John C Byrd; Richard R Furman; Steven E Coutre; Ian W Flinn; Jan A Burger; Kristie A Blum; Barbara Grant; Jeff P Sharman; Morton Coleman; William G Wierda; Jeffrey A Jones; Weiqiang Zhao; Nyla A Heerema; Amy J Johnson; Juthamas Sukbuntherng; Betty Y Chang; Fong Clow; Eric Hedrick; Joseph J Buggy; Danelle F James; Susan O'Brien
Journal:  N Engl J Med       Date:  2013-06-19       Impact factor: 91.245

9.  Discovery of dual inhibitors of the immune cell PI3Ks p110delta and p110gamma: a prototype for new anti-inflammatory drugs.

Authors:  Olusegun Williams; Benjamin T Houseman; Eric J Kunkel; Brian Aizenstein; Randy Hoffman; Zachary A Knight; Kevan M Shokat
Journal:  Chem Biol       Date:  2010-02-26

10.  The p110 delta structure: mechanisms for selectivity and potency of new PI(3)K inhibitors.

Authors:  Alex Berndt; Simon Miller; Olusegun Williams; Daniel D Le; Benjamin T Houseman; Joseph I Pacold; Fabrice Gorrec; Wai-Ching Hon; Yi Liu; Christian Rommel; Pascale Gaillard; Thomas Rückle; Matthias K Schwarz; Kevan M Shokat; Jeffrey P Shaw; Roger L Williams
Journal:  Nat Chem Biol       Date:  2010-02       Impact factor: 15.040
View more
  4 in total

Review 1.  Synthetic Lethality through the Lens of Medicinal Chemistry.

Authors:  Samuel H Myers; Jose Antonio Ortega; Andrea Cavalli
Journal:  J Med Chem       Date:  2020-11-02       Impact factor: 7.446

Review 2.  Overcoming Ibrutinib Resistance in Chronic Lymphocytic Leukemia.

Authors:  Bartosz Puła; Aleksandra Gołos; Patryk Górniak; Krzysztof Jamroziak
Journal:  Cancers (Basel)       Date:  2019-11-21       Impact factor: 6.639

3.  Unusual rearrangement of imidazo[1,5-a]imidazoles and imidazo[1,2-b]pyrazoles into imidazo[1,5-a]pyrimidines and pyrazolo[1,5-a]pyrimidines.

Authors:  Khadija Gambouz; Mohsine Driowya; Mohammed Loubidi; Zahira Tber; Hassan Allouchi; Saïd El Kazzouli; Mohamed Akssira; Gérald Guillaumet
Journal:  RSC Adv       Date:  2019-09-16       Impact factor: 4.036

4.  QSAR analysis on a large and diverse set of potent phosphoinositide 3-kinase gamma (PI3Kγ) inhibitors using MLR and ANN methods.

Authors:  Fereydoun Sadeghi; Abbas Afkhami; Tayyebeh Madrakian; Raouf Ghavami
Journal:  Sci Rep       Date:  2022-04-12       Impact factor: 4.379
  4 in total

北京卡尤迪生物科技股份有限公司 © 2022-2023.